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Impact of histopathology, tumor-infiltrating lymphocytes, and adjuvant chemotherapy on prognosis of triple-negative breast cancer

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Abstract

Background

Given its high recurrence risk, guidelines recommend systemic therapy for most patients with early-stage triple-negative breast cancer (TNBC). While some clinicopathologic factors and tumor-infiltrating lymphocytes (TILs) are known to be prognostic in patients receiving chemotherapy, their prognostic implications in systemically untreated patients remain unknown.

Methods

From a cohort of 9982 women with surgically treated non-metastatic breast cancer, all patients with clinically reported ER-negative/borderline (≤10%) disease were selected for central assessment of ER/PR/HER2, histopathology, Ki-67, and TILs. The impact of these parameters on invasive disease-free survival (IDFS) and overall survival (OS) was assessed using Cox proportional hazards models.

Results

Six hundred five patients met the criteria for TNBC (ER/PR < 1% and HER2 negative). Most were T1–2 (95%), N0–1 (86%), grade 3 (88%), and had a Ki-67 >15% (75%). Histologically, 70% were invasive carcinoma of no special type, 16% medullary, 8% metaplastic, and 6% apocrine. The median stromal TIL content was 20%. Four hundred twenty-three (70%) patients received adjuvant chemotherapy. Median OS follow-up was 10.6 years. On multivariate analysis, only higher nodal stage, lower TILs, and the absence of adjuvant chemotherapy were associated with worse IDFS and OS. Among systemically untreated patients (n = 182), the 5-year IDFS was 69.9% (95% CI 60.7–80.5) [T1a: 82.5% (95% CI 62.8–100), T1b: 67.5% (95% CI 51.9–87.8) and T1c: 67.3% (95% CI 54.9–82.6)], compared to 77.8% (95% CI 68.3–83.6) for systemically treated T1N0. Nodal stage and TILs remained strongly associated with outcomes.

Conclusions

In early-stage TNBC, nodal involvement, TILs, and receipt of adjuvant chemotherapy were independently associated with IDFS and OS. In systemically untreated TNBC, TILs remained prognostic and the risk of recurrence or death was substantial, even for T1N0 disease.

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Funding

This work was supported by the Mayo Clinic Center for Individualized Medicine; the Mayo Clinic Cancer Center (Grant Number CA15083-40A2 to MPG, JNI); George M. Eisenberg Foundation for Charities; the Mayo Clinic Breast SPORE (Grant Number P50CA 116201-9 to MPG, FJC, JNI, DWV, MP, KRK); and NIH Grant R01CA192393.

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Authors and Affiliations

  1. Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Roberto A. Leon-Ferre, Judith A. Gilbert, Minetta C. Liu, James N. Ingle & Matthew P. Goetz

  2. Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    Mei-Yin Polley, Heshan Liu, Victoria Cafourek, David W. Hillman, Jenna Lilyquist, Abigail Thomas, Krishna R. Kalari & Fergus J. Couch

  3. Hematology/Oncology, Roswell Park, Buffalo, NY, USA

    Ahmed Elkhanany

  4. Graduate School of Biomedical Science, Mayo Clinic, Rochester, MN, USA

    Margaret Akinhanmi

  5. Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Jenna Lilyquist, Vivian Negron, Fergus J. Couch & Daniel W. Visscher

  6. Surgery, Mayo Clinic, Rochester, MN, USA

    Judy C. Boughey

  7. Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA

    Matthew P. Goetz

Authors
  1. Roberto A. Leon-Ferre
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Corresponding author

Correspondence to Matthew P. Goetz.

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Conflict of interest

Roberto A. Leon-Ferre, Mei-Yin Polley, Heshan Liu, Judith A. Gilbert, Victoria Cafourek, David W. Hillman, Ahmed Elkhanany, Margaret Akinhanmi, Jenna Lilyquist, Abigail Thomas, Vivian Negron, Judy C. Boughey, Minetta C. Liu, James N. Ingle, Krishna R. Kalari, Fergus J. Couch, Daniel W. Visscher, and Matthew P. Goetz declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The need for obtaining informed consent was waived by the institutional review board, given that this study was retrospective and non-interventional.

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Leon-Ferre, R.A., Polley, MY., Liu, H. et al. Impact of histopathology, tumor-infiltrating lymphocytes, and adjuvant chemotherapy on prognosis of triple-negative breast cancer. Breast Cancer Res Treat 167, 89–99 (2018). https://doi.org/10.1007/s10549-017-4499-7

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